ABSTRACT Antarctic marine sponges are essential components of the benthic fauna, playing a crucial role both through their own biological activities and their symbiotic relationships with diverse microorganisms. Yet, the transcriptional repertoire and the immune responses associated with interactions with microorganisms in this unique environment still need to be fully understood. Here, we investigated the transcriptional repertoire underlying the immune system processes of the Antarctic sponge Myxilla ( Burtonanchora ) lissostyla . We generated a de novo transcriptome and functional annotation for M. ( B. ) lissostyla , collected during the austral summer of 2019, 2020, and 2021. Our findings revealed an extensive transcriptional repertoire with a high and consistent expression of constitutive transcripts across the years. Key pathways related to immune response and homeostasis were the most expressed in the Antarctic sponge transcriptome, and a diverse array of immune receptors highlights the wide host immune repertoire. Low microbial abundance sponges share a vast repertoire of immune receptors, and a predominance of membrane‐bound PRRs was detected mainly in M . ( B. ) lissostyla , indicating a broad range of receptors available for initial interactions and engagement with microorganisms. The functional repertoire unveiled here establishes baselines for assessing potential functional changes that may arise due to climate change.