There's a lot of good information above, and the point has already been made that the choice depends on the threat and the situation. So I'll try to come at it from a slightly different direction. I started as a wildlife biologist and although I've long been in management, I still get out on a lot of project sites to get things started and still directly supervise numerous field biologists. Some of that work happens on remote sites, and some of it happens at night. We're required to write a safety plan prior to starting each project, which kind of focuses the analysis.
First, with adequate preparation there are only a few parts of the continental US where I'd be very concerned about wildlife. I understand about fear of the unknown, as a scientist I don't have that to fall back on. If you think about it, in much of the eastern half of the country where the majority of the population lives, there's nothing larger than coyote and deer out there. I'd be more concerned about two-legged threats there, anything wildlife related could probably be handled with a light, small caliber trail gun. I'm about to get a team started on a project in Illinois and there's really nothing four-legged there that I'm worried about.
Where I live, on the northern California coast, black bear and mountain lion are relatively common. However attacks on humans are very rare (for example, see
https://www.sfgate.com/sports/articl...as-3139245.php ). Dive deep into the stats and most of those negative interactions are around tourist-heavy parks where idiots feed the wildlife and bears lose their fear of humans. In my county and the adjacent counties I can't find a single verified attack in recent decades. Of all my biologist friends... as past president of the local chapter of The Wildlife Society I know a lot of them... only one has ever had a negative interaction which in that case resulted in her being treed for a short time til backup arrived. That was on active timberlands, so who knows maybe the bear was pissed that it's home had just been destroyed. I'm not entirely kidding, if most local shelter had been removed and food was suddenly scarce, she may have encountered a very hungry and grumpy bear. My personal encounters with bear have almost always been glimpses of the back end of an animal rapidly departing the area. Big cat sightings are relatively unusual because they have such huge home ranges, while some of those animals especially at night acted like a big disdainful haughty cat they still all departed, just not always as quickly as a typical bear. I will say it gets the adrenaline pumping when encountering a big cat in the dark on a trail at a few tens of feet distance. That said, we're usually far more worried about skunk out for a night time walk, and need to go around those pretty regularly.
In this area the biggest threats are typically humans and dogs associated with illegal grows, or with homeless camps. I tend to carry a 3-inch 357 or a 9mm semi around here. The revolver is preferred in the backcountry in part because I can easily change out street ammo for non-lead (to stay fully compliant with state regs), and then back again on the way out. It used to be a GP-100, more recently I've gone to a 3-inch Colt King Cobra which I shoot slightly better and which is also lighter and easier to conceal.
Two counties to the south feral pigs start to become a possibility, and that can influence the choice of firearm and caliber.
In the interior mountain west where brown bear may be present, then I'll go with a 4-inch 625 mountain gun in 45 Colt and a 255gr Keith @ 900fps load, or occasionally a 4-inch 29-2. I sometimes also carry the mountain gun here in California just because.
Note that I haven't said anything about snakes. That's because working biologists respect them but aren't afraid of them. On Arizona projects I've encountered an average of two or three western diamondbacks and Mojave rattlers a day... during endangered species clearance surveys when we walked an average of 13 miles per day on transects through creosote bush scrub... and walked around snakes, maybe took a photo or two. The majority of snakebites in the US happen to drunken losers taking a dare to kiss a snake, to people keeping them as pets who get careless just once at feeding time, or equally stupid variants. Don't touch the snake and there's very little risk. In high density habitat, wear good boots and walk around the occasional encounter and the risk is nil.
Most of the time our safety plans identify things like ticks, heat or cold, and slips-trips-falls as the greatest risks. I've had people in the field almost every day for the past 32 years, most of those folks aren't carrying anything stronger than bear spray, and we've never had a wildlife related injury. So as always pay attention, but don't overthink the wildlife stuff at least in most of the US. Be more careful in brown bear country, and in other parts of the world with big game.