"They"
What we can surmise about "Them" is mostly taken from rumor and the cryptic Arilou. We know that the Androsynth civilization was attempting to harness Dimensional Fatigue technology, and was then completely wiped out by an unknown force. The Arilou intimated that this may have been because the Androsynth exposed themselves to "Them", and warned The Captain about Humans following suit.
The Arilou let on that much of what they have been doing to humans is "changing their smell", whatever that means, to protect them.
"They" are probably also the cause for Bukowski going mad on Eta Vulpeculae II and might even be the cause of some of his physical injuries.
Some believe that "They" are none other than the Orz. This conjecture is based upon the Orz's comments on the "smell" of humans, their present location (in old Androsynth space) and their reactions when questioned about the Androsynth.