In the early Church when everyone spoke Greek, the name Jesus was abbreviated to its first three letters, IHS. When the West converted to Latin with Jerome, they kept IHS with a handful of other Greek idioms (ICHTHUS, Kyrie Eleison, blah blah) even though most people had no idea what they meant. So, the I and the S were transfigured into Iesus and Salvatore (I forget if that's the right spelling), but the H was kept as posterity for whatever reason. Around the Reformation, people started making fun of it as a middle initial, since nobody could figure out what else it could mean.
Edit: I forgot to mention that there's a geek joke I heard long ago, saying that it stands for "Haploid". The joke being that he was formed with only a mother, so he has only one set of genetic data within him and thus he's haploid, as aposed to diploid like all normal mammals.