According to the HandBrake docs (ISTR) mp4 can't handle multiple languages and subtitle sets, so the conversion mkv->mp4 is (potentially) lossy. I'm no expert, just trying to keep the language/subtitle sets I want, maybe I've missed something here. What I do so far is HB encode to Matroska, not MPEG-4. Then I don't lose any of the ones I want. Also I have noticed sometimes MakeMKV is not entirely inclusive in its defaults and I have to add extra languages/subtitles.