RNA-seq provides a wealth of information about the genetic makeup and physiological state of targeted tissues or organs. We provide an overview of current uses of transcriptomes to study of differential gene expression in response to environmental challenges. Differential gene expression is commonplace and multidimensional. Kidney transcriptomes across a precipitation gradient, for example, diverge in multiple genes related to water conservation, but also in genes involved in detoxification and immune responses. A special case of differential expression is the co-option of functionally relevant genes for their ectopic expression in novel organs. Associations between differential gene expression and genetic divergence can be established, but genotyping transcriptomic data present several challenges, including paralogy, alternative splicing, and differential allele expression. Our study of kidney transcriptomes shows that genetic divergence varies broadly across genes, but tends to be larger in differentially expressed genes than in the remaining loci.