Which pressure mode of operation has the most stress on aircraft frame
Isobaric mode causes the most stress if you keep the cabin pressure and climb higher and higher. (Because the delta pressure and thus the forces become higher and higher)
That's why at high altitudes the isobaric mode is no longer used and the cabin pressurization switches to constant differential pressure instead, which limits the maximum stress.
And unpressurized, well that is not really stressing the hull at all