The first one is notoriously uncompromising and will allow the player to get stuck. Lack of supplies, strict time limits, oddly translated dialogue, and roving pockets of plague gas can all completely ruin your entire playthrough, forcing you to load an earlier save or just die. Also a lot of characters will outright lie to you, sending you off on wild goose chases you'd only know about if you chanced your way into seeing through their lies or you've played the game before. Since you'll barely have time to spare, you sometimes can't afford to assume someone's lying to you.

2 is much more relaxed from what I've played. Much smoother experience really. Pathologic 1's difficulty is more rooted in clunkinesss, poor translations, and frequent save scumming.