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Toxicokinetics is the movement and fate of chemicals in the body and is dictated by chemical uptake, distribution, metabolism, and excretion. When exposed to foreign chemicals, animals respond by upregulating genes that work to detoxify and eliminate the substance. In fish, we know little about the major chemical defense genes, their regulation, and the tissue-specific patterns of gene expression. Chemical defense is coordinately regulated across major organs such as the gills, intestines, liver, and kidney. Yet, most fish studies have focused primarily on a few chemical defense genes within the liver. My research explores this gap in knowledge by determining the expression of the gene families involved in chemical defense across organs significant to toxicokinetics and in response to specific chemicals in the well-established zebrafish model (Danio rerio). Using existing transcriptomics data, I have examined the basal expression of the chemical defensome gene families in the gut and gills of unexposed male zebrafish. The raw reads were analyzed using two different pipelines to understand how the output from pseudo-mapping and quantification of estimates differs from the use of splice-aware mapping and read counting tools. The GO enrichment analysis revealed that the gut upregulated defensome genes related to xenobiotic stimulus, detoxification, sulfation, and various metabolic processes. The gill upregulated responses to temperature stimulus, heat, oxidative stress, and protein folding. Although both the gills and intestines play critical roles in chemical uptake, our preliminary RNA-seq analysis suggests that the intestine has a greater ability to respond and metabolize chemicals. Importantly, impacts on underlying gene expression have the potential to determine the animal’s ability to metabolize and remove chemicals from their system and may alter adverse effects of chemical exposure.