I'm intrigued by the idea of humans with feathered wings as a 6th appendage, but with prolonged flight, if such a thing were actually possible for humans naturally as it is in my book, I'm not sure which muscles would become sore over long periods with little rest between, especially for newer fliers, or people unaccustomed to those long distances. As it would be with any other type of muscle fatigue there is the expected amount of soreness and weakness, shaky legs or burning and cramping, but which muscle group would this affect? Feel free to elaborate, anything and everything will help.
The muscles would have to be just as imaginary as human wings themselves are, you would need to develop a new set of muscle groups, analogous to those we use for our arms, but with more focus on performance in a single plane (the direction of beating).
In addition to these imaginary muscle groups, your core muscles (Thoracic and abdominal) would likely fatigue as well, not to mention your heart and lungs from the level of activity that would need to be sustained.
You'd also likely have to lighten the skeleton, and that would be very risk from an evolutionary standpoint as humans rely heavily on their strong bones for survival.