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Abstract While vertebrate immune systems are appreciated for their complexity and adaptability, invertebrate immunity is often considered to be less complex. However, immune responses in many invertebrates likely involve sophisticated processes. Interactions between the crustacean hostDaphnia dentiferaand its fungal pathogenMetschnikowia bicuspidataprovide an excellent model for exploring the mechanisms underlying crustacean immunity. To explore the genomic basis of immunity inDaphnia, we used RNA‐sequencing technology to quantify differential gene expression between individuals of a single host genotype exposed or unexposed toM. bicuspidataover 24 h. Transcriptomic analyses showed that the number of differentially expressed genes between the control (unexposed) and experimental (exposed) groups increased over time. Gene ontology enrichment analysis revealed that differentially expressed genes were enriched for immune‐related molecules and processes, such as cuticle development, prostaglandin, and defense response processes. Our findings provide a suite of immunologically relevant genes and suggest the presence of a rapidly upregulated immune response involving the cuticle inDaphnia. Studies involving gene expression responses to pathogen exposure shine a light on the processes occurring during the course of infection. By leveraging knowledge on the genetic basis for immunity, immune mechanisms can be more thoroughly understood to refine our understanding of disease spread within invertebrate populations.