Blurring transhumanism with cyberpunk gives species that were formerly human, but so many steps removed as to be completely alien to one another. A setting set a century-plus into the future, where mankind has travelled to asteroids and sea-beds, could have gene-altered species indistinguishable from extraterrestrials. Palladium Books' Mechanoids trilogy basically takes this approach. The original Mechanoids were gene-modded human cyborgs who continued to alter themselves in both aspects. When they eventually returned to their homeworld they were reviled as monsters.