Fluorescent light (FL) has become a common artificial light source under which animals, including humans, spend increasing amounts of time. Although the solar spectrum is quite dissimilar in both wavelengths and intensities, the genetic consequences of FL exposure have not been investigated. Comparative RNA-Seq studies establish expression patterns within skin, brain, and liver for Danio rerio (zebrafish), Oryzias latipes (medaka), and the hairless mouse (Mus musculus) after exposure to FL. The skin and brain of the three animal species as well as the liver of both fish models all exhibit increased inflammation and immune responses; however, the mouse liver suppressed the same pathways. Overall, the conserved nature of the genetic responses observed after FL exposure, among fishes and a mammal, suggest the presence of light responsive genetic circuitry deeply embedded in the vertebrate genome.