The rising demand for nutritious and low-fat foods has made aquaculture one of the fastest-growing food industries worldwide. Inland finfish aquaculture operations produce wastewater high in phosphorus from uneaten feed and ammonia from nitrogenous excretions. Northern wild rice (Zizania palustris), a nutritious and valued wetland crop, benefits from large quantities of phosphorus and ammonia-based nitrogen. Applying aquaculture wastewater (AWW) as a fertilizer for wild rice paddies presents a sustainable system for the recycling of nutrient rich wastewater while supporting optimal plant growth. Yet, introducing uncharacterized wastewater to an ecosystem presents substantial ecological risks. This includes the addition of ammonia, which is toxic at low concentrations, and phosphorus, which can contribute to eutrophication resulting in oxygen depletion within aquatic ecosystems. In Chapter 2, we assessed the ecotoxicological effects of adding aquaculture wastewater to an aquatic ecosystem using targeted transcriptomics with liver tissues of adult fathead minnows (FHM; Pimephales promelas) chronically exposed to incremental additions of AWW in simulated wild rice paddy mesocosms (n = 16). In Chapter 3, we assessed the effects of chronic nitrogen and phosphorus exposures, at concentrations relevant to AWW applications, on the health and cellular stress response of FHMs using non-targeted proteomics on mucus and liver tissues from FHMs exposed for 30 days in the laboratory. The objective was to determine if adequate nutrient loadings would adversely impact fishes in the ecosystem. We found that increasing quantities of AWW and nutrients did not cause lethality or affect morphometric endpoints, however oxidative stress, immunological, and metabolic responses were observed in both transcriptomic and proteomic evaluations of liver tissues. Mucus proteins were not effective in detecting cellular stress responses between treatments, however temporal trends were observed. Environmentally-relevant AWW and nutrient exposures were sufficient to elicit cellular stress responses, however, this concentration would likely not be great enough to impair the health and survival of FHMs. This study may aid in understanding the ecotoxicity of aquaculture wastewater effluent and may further develop the use of mucus in omic analyses to limit lethal sampling in biological and ecotoxicological research.