**1. Introduction**

Ricin toxin, derived from the castor bean plant Ricinus communis, is a highly toxic protein that belongs to the type 2 ribosome-inactivating protein (RIP) family [1,2]. The catalytically active subunit of ricin translocates into the cell cytoplasm where it causes irreversible inhibition of protein synthesis and ultimately cell death [3]. Several methods for developing simple, reliable, and sensitive detection approaches towards ricin have been studied [4] While many of the methods for ricin detection are robust, each has limitations in selectivity, and no single approach is currently able to fully distinguish ricin from other harmful toxins [4].

MicroRNAs (miRNAs) are small, endogenous RNA molecules, 21–24 nucleotides (nt) long. They play an important regulatory role by inducing posttranscriptional gene silencing of their mRNA targets, and thereby function as negative gene expression regulators. miRNAs contribute to the regulation of most biological processes and also influence numerous pathological states, including atherosclerosis [5], kidney diseases [6], cancer, and infectious disease [7]. Several features of miRNAs render them ideal biomarkers for toxicology. These include improved stability in biofluid samples [8], tissue specific patterns of expression [9], and highly-developed multiplexing measurement methods [10]. Although various approaches towards developing simple, reliable, and sensitive methods for ricin detection have been investigated [4,10], miRNAs have been underexplored. In this study, we aimed to examine changes in the miRNA expression profile in mice following pulmonary ricin intoxication, and the application of these changes to ricin detection. We assumed that differentially expressed

miRNAs will enhance our understanding of the ricin toxicity mechanism and may be used for intoxication. We detected significant changes in miRNA expression levels following ricin exposure, including distinct enrichment of innate immunity related miRNAs. Gene expression analysis further corroborated these results, and revealed the activation of several immune regulation pathways and immune cell recruitment after ricin exposure. We believe the changes revealed following ricin exposure will set the ground for a better understanding of the intoxication process.
