Is this possible? In my 2+ years using this program, I have never found a use for this odd feature. It's only ever caused me annoyance when accidentally saving a file with a channel or two disabled, when what I want is to always save with all channels enabled. Furthermore, it's annoying when muting and unmuting channels counts to the program as a change, which sometimes makes me forget if I actually changed anything that I might want to save.
Further information: I use OpenMPT to write music for my games, which I then use directly in IT format. There are a few things for which I have the game engine fade channels in and out to create effects (think Yoshi's bongo tracks in Super Mario World), but this only works if the IT file I give it has all of its channels enabled. However, channel muting/unmuting is a great way in-program to test these effects, and I'll often leave them disabled without realizing it, only to test it in-game later and realize I left the channel off when the effect doesn't work.
No, that's currently not possible.
I do like the idea though. +1 from me.
As of r7307, there is a hidden setting "Misc.SaveChannelMuteStatus" which can be used to disable saving of muted channels in IT/MPTM/S3M files.