My BP, Ralph, is super sweet and calm. Yet even he sometimes lets out a hiss when I lift his hide or pick him up unexpectedly.
I feel it is the ball python equivalent to "MOMMM I DON'T WANNA GO TO SCHOOLLLL" haha. Like a simple objection to the situation. Or sometimes just cause they're surprised. I try to make my presence known to my snake before I interact with him so he knows what to expect.