How cells maintain mRNA homeostasis during changes in size remains poorly understood, particularly in rapidly adapting immune cells. This study investigated mRNA metabolism in RAW264.7 macrophages and primary B cells following LPS activation. Both cell types showed increased volume after stimulation. In RAW264.7 cells, Poly(A) FISH mean intensity remained constant while the total signal increased with cell volume, indicating stable mRNA concentration. In contrast, B cells showed increases in both mean and total Poly(A) FISH staining intensity, suggesting elevated mRNA concentration. 5EU labelling revealed massive reduction in nascent transcription from RAW264.7 cells but increased nascent transcription in B cells, reflecting divergent transcriptional responses to immune activation. Results from RNA StrandBrite staining and Trizol-based RNA extraction from RAW264.7 showed only a modest drop in total RNA despite a strong reduction in nascent transcription, suggesting reduced RNA degradation plays a compensatory role. These findings reveal distinct strategies for RNA homeostasis and highlight the importance of RNA degradation in maintaining transcript levels during immune activation.